This application is for the continuation of the NIH Exploratory Trials in Parkinson's Disease (NET-PD). NETPD was designed to enroll patients in a series of pilot studies and clinical trials of new agents for the treatment of Parkinson's Diseas (PD). The role of the clinical sites is to identify, screen, enroll, treat, and follow patients in hese trials as well as report data in a timely manner to the data coordinating center and to report adverse efects among enrolled patients. The recruiting sites will provide high quality clinical assessments, data entry and management and meet all regulatory statutes outlined for the trials. Currently, NET-PD is conducting the LS-1 study, a multi-center, double blind, phase III clinical trial designed to determine whether or not creatine is more effective than placebo in slowing the decline in PD patients with early, treated PD. Enrollment began in 2007 and closed in May of 2010. The key focus is to continue longitudinal assessment of subjects, ensuring maximum retention. Another exploratory NET-PD trial has recently begun enrolling patients. A multi-center, double-blind, placebo-controlled phase II study of pioglitazone in early PD assesses the impact of pioglitazone on the progression of PD as well as the efficacy, safety and tolerability. Enrollment began in 2012 and is expected to continue through 2015. The Neurology programs at the University of Vermont College of Medicine (UVM/COM-Site 137) and Dartmouth-Hitchcock Medical Center (DHMC-Site 155) have demonstrated the ability to integrate their efforts and to work collaboratively in this region to provide excellent clinical cae and seamless integration of the research goals of NET-PD. Collectively, our consortium have enrolled 58 patients in LS1 and expect to reach our target for FS-ZONE by August of 2012. In addition, we have excellent retention of subjects on therapy (top 10%). Our programs are working to enhance, as well as sustain, efficacy so that we will remain a major contributors to NET-PD.